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INVESTIGACIÓN EN PSIQUIATRÍA DEL NIÑO Y DEL ADOLESCENTE Celso Arango M.D., Ph.D [email protected] 25 de mayo de 2010 www.hggm.es/ua www.cibersam.es Criterios nosológicos en psiquiatría. Limitaciones “La extraordinaria diversidad de los cuadros clínicos que corresponden a un mismo trastorno básico, demuestra que las condiciones de su puesta en marcha deben ser muy complejas. Incluso cuando un trauma externo muy concreto, como una herida en la cabeza, o una intoxicación, son los responsables de la aparición de un cuadro clínico, este cuadro deja comprobar numerosos factores históricos y personales. La estructuración general del sistema nervioso, la predisposición del sexo, y el destino personal del enfermo hacen, todos juntos, que este cuadro sea característicamente personal" Kraepelin, 1919 Concepto de enfermedad/trastorno mental Enfermedades frente a trastornos Desventaja biológica Método empírico-estadístico Definición de Trastorno Mental El Trastorno mental viene definido no sólo por la presencia de síntomas y/o la desviación de la conducta normal, sino porque bajo tales fenómenos subyacen mecanismos que comportan una restricción de libertad. Existe una pérdida de las posibilidades de autorrealización y una clara interferencia en la vida cotidiana del paciente y en sus relaciones interpersonales. Ciencia, filosofía y psiquiatría “La psiquiatría se preocupa de áreas de la experiencia y comportamientos humanos como la emoción, deseos, voluntad y creencias con gran carga de valores” Bill Fulford “Si el cerebro fuese tan simple que nosotros pudiésemos comprenderlo, nosotros seríamos tan simples que no lo entenderíamos” Albert Einstein Fundamentos de la psiquiatría Toda la medicina clínica es parte Ciencia y parte Arte. El Arte consiste en adaptar el conocimiento científico a las necesidades particulares de un paciente. Fundamentos de la psiquiatría “ Si la especialidad de psiquiatría resiste lo suficiente en sus esfuerzos actuales puede encontrarse algún día ante los trastornos de personalidad y las listas de síntomas con la misma nostalgia con la que ahora mira la medicina basada en el diván” Editorial, Science 31 de octubre de 2003 Causas de los Trastornos mentales Factores predisponentes (vulnerabilidad): ¿Por qué enferma? Factores precipitantes o desencadenantes ¿ Por qué ahora? Factores de mantenimiento: ¿Por qué se mantiene? IMPACT OF MENTAL DISEASES Maternal conditions Respiratory infections Malaria Childhood diseases Diarrhoeal diseases HIV/AIDS Tuberculosis Other CD causes Injuries Congenital abnormalities Musculoskeletal diseases Perinatal conditions Nutritional deficiencies Other NCDs Malignant neoplasms Diabetes Neuropsychiatric disorders Sense organ disorders Cardiovascular diseases Respiratory diseases Digestive diseases Diseases of the genitourinary system Disease burden measured by Disability Adjusted Life Years (DALYs) Source: WHO 2005 Global Inability: 15-44 years Mental illness: Main cause for Disability in Young Adults Anemia Schizophrenia Violence Years of healthy life lost Wars Bipolar disorder Self-injury Alcohol use Traffic accidents Tuberculosis Mayor depression 0 12500 25000 37500 50000 Years of life with disability adjusted; thousands DALYs = One DALY is equal to one day of healthy life lost. Murray Cl, Lopez AD, editors. The Global Burden of Disease. Harvard University Press, 1999. Porcentaje estimado del porcentaje de AVAD por causa sobre el total. España 2000. Instituto de Salud Carlos III Enfermedades no transmisibles 86% Accidentes y lesiones 8,6% Enfermedades transmisibles, maternales, perinatales y nutricionales 5,4% Fuente: Área Salud Internacional. ISCIII COVERED AREAS OF KNOWLEDGE IN THE NETWORK DEPRESSION EPIDEMIOLOGY CLINICAL RESEARCH NEUROPSYCOPHARMACOLOGY POST-MORTEM STUDY BIOCHEMISTRY GENETICS NEUROIMAGING DEPRESSION IN CHILDREN AND ADOLESCENTS PSYCHOGERIATRICS SCHIZOPHRENIA EPIDEMIOLOGY CLINICAL RESEARCH NEUROPSYCOPHARMACOLOGY GENETICS NEUROIMAGING PSYCHOSIS IN CHILDHOOD AND ADOLESCENCE PSYCHOSOCIAL FACTORS COMORBIDITY BIPOLAR DISORDER EPIDEMIOLOGY CLINICAL RESEARCH NEUROPSYCOPHARMACOLOGY GENETICS NEUROIMAGING NEUROPSYCHOLOGY PSYCHOSIS IN CHILDHOOD AND ADOLESCENCE PSYCHO-EDUCATION FUNCTIONAL ADAPTATION Paus et al., Nature Neuroscience 2008 Salud Mental Infanto-Juvenil Unidad de Adolescentes UNIDAD DE ADOLESCENTES DPTO. PSIQUIATRIA H. G .U. G. MARAÑON www.hggm.es/ua/ www.cibersam.es ASISTENCIA, INVESTIGACIÓN, DOCENCIA INVESTIGACIÓN CLÍNICA AMBULATORIO AMI-TEA INGRESO HOSPITALARIO PEP PRIMEROS EPISODIOS PSICÓTICOS, PEP NEUROPSICOFARMACOLOGÍA DEL DESARROLLO COGNICIÓN EN TRASTORNOS DEL NEURODESARROLLO NEUROBIOLOGÍA DE LOS TGD GENÉTICA TGD BIOQUÍMICA TRATAMIENTO GRUPAL NEUROPSICOLOGÍA ADOLESCENTES ANTIPSICÓTICOS INFANCIA ADOLESCENCIA FAMILIARES PEP ALTO RIESGO NEUROIMÁGEN ANTIOXIDANTES REHABILITACIÓN COGNITIVA INTRODUCTION The first episode of psychosis is a critical period in the course of each patient’s illness and perhaps the most important opportunity for therapeutic intervention Even at Conversion to Psychosis might be a critical point Adapted from Pantelis C et al. Lancet. 2003;361:281 Why to study EOP: • Early-onset psychotic disorders (EOP, onset prior to 18 years) are more severe and disabling than those beginning in adulthood (Ballageer et al. 2005; Volkmar, 1996) • EOP has usually an insidious onset with symptomatic overlap between different diagnoses, starting during a crucial period in development (Menezes and Milovan, 2000) • Although EOP can be diagnosed with the adult criteria, specific ethiopatological, prognostic, diagnostic and treatment features need to be further studied (Arango et al, 2004) • Few studies of first-episode EOP: ethical concerns, difficult recruitment…Previous studies: assessment and sample limitations (Nicolson et al, 2000; McKenna et al.1994; McClellan et al. 2002) Advantages of Studying First- episode EOP • Methodological advantages: – less confounding variables (adverse life events, exposure to drugs or medications, effect of progression of illness) – more homogeneous sociodemographic factors (most attend compulsory school) – higher genetic loading • Study of EOP may clarify etiology and prognosis of the different psychotic disorders Relevance of findings in normal brain development for the neurodegenerative vs. neurodevelopmental hypotheses Thompsom et al., 2001 Diagnostic stability of first-episode EOP DSM-IV diagnoses Follow-up Positive predictive value (%) Baseline (N=24) 1-yr FU (N=24) 2-yr FU (N=23) B to 1-yr FU 1-2 yr FU B to 2-yr FU Schizophrenia 16.7% 33.3% 33.3% 100 100 100 Bipolar Disoder 29.2% 37.5% 33.3% 71.4 100 71.4 Schizoaffective disorder 8.3% 8.3% 8.3% 50.0 100 50.0 Psychosis NOS 25.0% 8.3% 4.2% 16.7 50 16.7 Schizophreniform/ brief psychosis 16.7% 8.3% 12.5% 50.0 100 50.0 Depression with psychotic features 4.2% 4.2% 4.2% 100 100 100 -Diagnostic stability was remarkably high for schizophrenia, moderate for bipolar disorder, and low for other diagnoses Fraguas et al. Child Psychiatry Hum Dev 2008; 39(2):137-45 INTRODUCTION Changes in neurocognitive outcomes over 2-years in first-episode EOP and controls LONGITUDINAL ASSESSMENT EOP (N=22) Controls (N=29) Attention F= 5.74 p= 0.02* F= 3.91 p= 0.05 Working memory F= 0.25 p= 0.61 F= 1.96 p= 0.17 Executive function F= 3.01 p= 0.09 F= 6.35 p= 0.01 Learning & memory F= 15.15 p= 0.001* F= 0.80 p= 0.37 Global F= 13.25 p= 0.002* F= 9.77 p= 0.004 * In EOP, significance disappeared when controlling for changes on symptomatology over the FU period Mayoral et al. Eur Psychiatry 2008; 23(5):375-83 NEURODEVELOPMENT Actual developmental theories: a subtle disease process affects critical circuits during early development..…remains clinically silent until the normal maturation of the affected structures brings the “lesion” to the symptomatic stage. NEURODEVELOPMENT * p ≤ 0.01 schizophrenia vs bipolar Parellada et al 2006 NEURODEVELOPMENT Desarrollo premórbido en esquizofrenia de inicio muy temprano Lenguaje 49 pacientes (<12) Datos retrospectivos Motor Social Area de alteración en el desarrollo Educational Nicolson et al., 2000 NEURODEVELOPMENT At least one psychomotor developmental deviance.- % p=0.069, schizophrenia vs bipolar Parellada et al 2006 NEURODEVELOPMENT IQ and academic achievement.- ** * ** * *p<0.05 vs controls **p<0.001 vs controls Corrected by parents´ studies patients vs controls achievement, OR=4 Parellada et al 2006 NEURODEVELOPMENT Abnormal dermatoglyphic patterns. Dissociations.- NEURODEVELOPMENT Controls (n=41) Patients (n=39) 5 (12.2) 9 (23.7) Controls Schizoph. Bipolar Other Males (n=57) 4 (14.8) 6 (42.9)* 2 (22.2) 1 (14.3) Females (n=21) 1 0 0 0 *OR=4.32, p=0.04, schizophrenia vs control Dissociations.• 13/14 dissociations were present in males (p=0.048) • None of the six schizophrenic patients with dissociations had a family history of psychosis (Fisher exact 0.093 bilateral, 0.058 unilateral) NEURODEVELOPMENT Neurological soft signs.Mean S.D. CONTROLS (n=47) PATIENTS (n=49) Pts. vs Controls Between groups Sch. vs controls Tot. NES 11.98 6.11 25.69 9.35 p<0.001 ns p<0.001 Sen. Int 2.68 2.10 5.22 2.75 p<0.001 ns p=0.001 SCMT 1.47 1.73 4.73 3.45 p<0.001 ns p<0.001 Motor Coord 2.06 1.48 3.78 2.2 p<0.001 ns p=0.02 Others 5.77 3.08 11.96 4.31 p<0.001 ns p<0.001 At least 2 NSS 71.1 95.9 p<0.01 ns p=0.07 All patients´ groups differed independently from controls Mayoral et al 2009 NEURODEVELOPMENT Changes in neurocognitive outcomes over 2-years in first-episode EOP and controls LONGITUDINAL ASSESSMENT EOP (N=22) Controls (N=29) Attention F= 5.74 p= 0.02* F= 3.91 p= 0.05 Working memory F= 0.25 p= 0.61 F= 1.96 p= 0.17 Executive function F= 3.01 p= 0.09 F= 6.35 p= 0.01 Learning & memory F= 15.15 p= 0.001* F= 0.80 p= 0.37 Global F= 13.25 p= 0.002* F= 9.77 p= 0.004 * In EOP, significance disappeared when controlling for changes on symptomatology over the FU period Mayoral et al. Eur Psychiatry 2008; 23(5):375-83 NEURODEVELOPMENT Brain volume differences between first-episode EOP and controls at baseline assessment -First-episode EOP (N=23) and healthy controls (N=37) -Duration of illness 13.91 (12.74) weeks Male patients showed: -Larger volumes in overall CSF (p = .044), and left frontal (p = .024), and right parietal sulci CSF (p = .042) -Lower volumes of GM in the right frontal (p = .012) and left frontal (p = .006) lobes No significant differences between different EOP diagnoses Moreno et al. J Am Acad Child Adolesc Psychiatry 2005; 44:1151-1157 NEURODEVELOPMENT Structural brain abnormalities in 92 children and adolescents with a recent-onset first episode of psychosis, and 94 healthy controls. Baseline evaluation In male patients: - GM volume was reduced in: whole brain (E.S.=0.77), frontal (0.98 and 0.79 in right and left) and parietal lobes (0.61 and 0.42). - Total CSF volume was increased (E.S.=0.81). - CSF was also increased in frontal, temporal, and right parietal lobes. Bipolar patients showed fewer differences than other diagnoses. Reig et al, in press Results (II) NEURODEVELOPMENT • Are local gray matter volumes different between patients who eventually develop schizophrenia or bipolar disorder? • Schizo – controls: Medial frontal • Schizo – controls: Left middle frontal • Bipolar – controls: Medial frontal • Others – controls: Insula Janssen et al JAACAP 2009 Even ‘early’ might already be too Late! Normal Subjects Subjects With Schizophrenia Difference P Value .00002 .0001 .0005 .001 .005 .01 .05 Adapted from: Thompson PM, et al. Proc Natl Acad Sci USA. 2001;98(20):11650-11655. Results (I) Gray matter volume abnormalities be detected in patients with recent-early-onset first episode psychosis? • Medial frontal cortex • Left middle frontal gyrus • • Left insula All brains in standard space, permitting localization of blobs. JAACAP 2009 Results (II) • Are local gray matter volumes different between patients who eventually develop schizophrenia or bipolar disorder? • Schizo – controls: Medial frontal • Schizo – controls: Left middle frontal • Bipolar – controls: Medial frontal • Others – controls: Insula JAACAP 2009 Progression of brain volume changes in firstepisode EOP and controls over 2-years SIGNIFICANT RESULTS: 1.2% 2.9% FRONTAL GRAY MATTER 0.7% 2.0% MALES Patients (n=16) Controls (n=21) Time x group p=0.02 Group P p<0.01 Group C p<0.05 Time x group p=0.02 Group P ns Group C ns In the frontal lobe, rate of GM volume loss was higher in EOP patients (L: 2.9 and R: 2.0%) than in Controls (L: 1.2 and R: 0.7%) Reig et al.. Schizophrenia Bulletin. 2009 Unpublished data Left Frontal GM Volume FEMALES MALES PAT VS CONT * BASAL PAT VS CONT * % CHANGE IN 2YR males: p = 0.0405 females: ns males: p = 0.0254 females p= 0.0240 * ANCOVA for differences between PAT and CONT using age and scanner as cofactors of no interest Rate of GM volume loss within the 2 yr follow-up was higher in patients (-3.3% ; -3.2% -for males and females respectively) than in controls (-0.7% ; -0.3% -for males and females respectively). Unpublished data Left Frontal CSF Volume FEMALES MALES PAT VS CONT * BASAL males: p = 0.0139 females: ns PAT VS CONT * % CHANGE IN 2YR males: p = 0.0050 Females p= 0.0195 * ANCOVA for differences between PAT and CONT using age and scanner as cofactors of no interest (Males) Significant increase of CSF volume within the 2 yr follow up (6.5% ; 5.4% -for males and females respectively), than in controls (2.3% ; 2.6% -for males and females respectively). 2 year followup spectroscopy study Longitudinal change Controls = 2.2 % Patients = 0.7 % Unpublished data ÂW|áxtáxá tyyxvà|Çz à{x }âäxÇ|Äx uÜt|Ç {täx ÅÉÜx ÑÉãxÜyâÄ xyyxvàá uxvtâáx à{xç wxáàÜÉç ÅtàâÜ|Çz à|ááâxáÊ à|ááâxáÊ Emil Kraepelin, The manifestations of Insanity, 1920 ∏ÂitÜ|Éâá wxäxÄÉÑÅxÇàtÄ áàtzxá Éy t ÅxÇàtÄ w|áÉÜwxÜ vÉÜÜxáÑÉÇw àÉ à{x zÜtwâtÄ xåàxÇá|ÉÇ Éy t ÅÉÜu|w ÑÜÉvxáá à{Éâz{Éâà ÅÉÜx tÇw ÅÉÜx tÜxtá Éy à{x uÜt|ÇÊ Emil Kraepelin, The manifestations of Insanity, 1920 RELATIONSHIP BETWEEN OXIDATIVE CELL DAMAGE AND BRAIN VOLUMES CONTROL N=78 SCHIZOPH N=26 BIPOLAR N=14 Intracranial volume B=-0.008, t=-0.647 (C.I. 95% B: -0.031 - 0.016) P=0.520 B=0.021, t=-0.644 (C.I. 95% B: -0.039 - 0.080) P=0.478 B=-0.057, t=-1.464 (C.I. 95% B: -0.148 - 0.035) P=0.187 Frontal grey matter B=0.003, t=0.321 (C.I. 95% B: -0.015 - 0.021) P=0.749 B=-0.013, t=-0.705 (C.I. 95% B: -0.050 - 0.025) P=0.490 B=-0.004, t=-0.161 (C.I. 95% B: -0.070 - 0.062) P=0.877 Parietal grey matter B=-0.005, t=-0.644 (C.I. 95% B: -0.022 - 0.011) P=0.521 B=-0.004, t=0.252 (C.I. 95% B: -0.040 - 0.032) P=0.804 B=-0.027, t=-1.070 (C.I. 95% B: -0.089 - 0.035) P=0.326 Temporal grey matter B=0.006, t=0.690 (C.I. 95% B: -0.011 - 0.022) P=0.492 B=-0.026, t=-0.966 (C.I. 95% B: -0.082 - 0.030) P=0.347 B=0.073, t=1.532 (C.I. 95% B: -0.043 - 0.189) P=0.176 Total sulcal CSF B=0.017, t=0.851 (C.I. 95% B: -0.022 - 0.056) P=0.398 B=0.006, t=0.146 (C.I. 95% B: -0.074 - 0.085) P=0.886 B=-0.015, t=-0.187 (C.I. 95% B: -0.215 - 0.185) P=0.858 Lateral ventricles B=0.003, t=0.076 (C.I. 95% B: -0.071 - 0.077) P=0.940 B=0.239, t=3.863 (C.I. 95% B: -8.141 - -1.997) P=0.001 B=0.021, t=0.098 (C.I. 95% B: -0.501 - 0.543) P=0.925 ± Regression analyses included brain volumes as dependent variables, and levels of LOOH, total intracranial volume (except for intracranial volume), age, gender, daily smoking status (as dichotomous variable yes/no), IQ, psychopathology (as total PANSS score; only for EOP patients), and time since onset of psychotic symptoms (only for EOP patients) as covariables. Significant value (P<0.0033, after Bonferroni correction) are in boldface. For statistical analyses brain volumes and LOOH were log-transformed Fraguas et al submitted Clusters of cortical thinning in first episode early onset schizophrenia Biol Psych 2009 Outcome and Progressive Brain Changes Ventricle / Brain ratio Ventricle Change Over 5 Years 1.7 Scan date 1.6 Year 1 Year 5 1.5 1.4 1.3 1.2 Left Ventricle Right Ventricle Kraepelinian Davis KL et al. Biol Psychiatry. 1998;43:783-793. Left Ventricle Right Ventricle Non-Kraepelinian EXPLORATORY ANALYSIS FOR PROGNOSTIC PREDICTION r = 0.769 (p = 0.0003) • Poor sensory integration: thalamus BJP 2009 • Poor motor coordination and sequencing of complex motor caudate nucleus poor acts: • We generate a t-map at t=3.22 (p<0.001) and after use small volume correction to test only voxels within ROIs. • Clusters of any size containing a voxel of p<0.05 corrected are considered statistically significant BJP 2009 Results – shape analysis – groupwise Shape differences in the thalamus, colored areas (not grey) indicate sigificant differences in thalamic shape • Left Right SubmItted 2010 Gyral and sulcal based cortical metrics: What constitutes the frontal lobe differences between patients Sulcal span and controls? A Superior frontal gyrus Superior frontal sulcus Sulcal depth Lateral Left Left Frontal - Anterior C C Kochunov et al 2008 Sulcal depth • Gyrus: • Thickness, surface, gyrification • Sulcus: • Sulcal span and sulcal depth • Male patients have less thickness, surface and gyrification in superior frontal gyrus • Male patients have larger sulcal span and shallower sulcal depth in superior frontal gyrus Longitudinal neuroimaging: 0-25 years What questions can we answer? I. Changes in connectivity Diffusion tensor imaging (DTI) allows for assessment of white matter connectivity. The pediatric use of antipsychotics has dramatically increased • In 2002, 93% of all antipsychotics were atypicals. • In 2004, 99% were atypicals. Cognition: Tasks grouped in cognitive domains Z-scores (SD) Executive functions 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0 -1.5 Quetiapine Olanzapine -2.0 Attention Working memory Executive Verbal fluencyVisuoconstructiveLearning and functioning ability memory • • No cognitive improvement was observed in any of the groups No differences between groups Robles et al 2009 Change in weight over time by treatment group olanzapine/quetiapine WEIGHT 80.00 75.00 WEIGHT 70.00 quetiapine 65.00 olanzapine 60.00 55.00 50.00 basal day 7 day 15 day 30 day 90 day 180 Arango et al, 2009 Metabolic side effects in young people treated with second-generation antipsychotics The aim of this study was to evaluate metabolic side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (RIS, OLZ, QTP) Sample: 66 patients antipsychotic-naïve (n=25) or quasi-naïve patients* (n=41). • Mean age=15.2 (SD=2.9), range 4-18 yr. • 66.7% male • 51.5% schizophrenia or other psychosis No baseline differences between treatment groups *Quasi-naïve patients: fewer than 30 days with any antipsychotic Fraguas et al, J Clin Psychiatry 2008 Metabolic side effects in young people treated with second-generation antipsychotics At risk for adverse health outcome BMI≥95 or BMI>85 + •hypertension >90th or •fasting cholesterol≥ 200mg/dl or •LDL cholesterol > 130 or •HDL cholesterol <40 or •TGC≥150 or •Hyperglycaemia ≥110 mg/dl) Significant weight gain Defined as > 0.5 increase in body mass index (BMI) z-score (adjusted for age and gender) at 6 months RIS: 50% OLZ: 75%* QTP: 29% At risk adverse Baseline 6 month RIS OLZ QTP 22.7% 15.0% 12.5% 36.4% 60.0%* 20.8% * p<0.05 • Total cholesterol increased in patients receiving olanzapine (p=0.047) and quetiapine (p=0.016). •Treatment with quetiapine was associated with a decrease in free thyroxin (p=0.011). *p<0.01 Fraguas et al, J Clin Psychiatry 2008 Abnormal Involuntary Movements -60 children and adolescents who had taken antipsychotic medication for less than one month and 66 who had been receiving treatment with antipsychotic for more than 12 months. - Age=15.62 (SD=1.85). Short-term exposure Long-term exposure Statistics Total dyskinesia score 2-9 27(45%) 52 (78.8%) χ²=10.241 p=0.002 Total dyskinesia score 10-19 0 5 (7.57) χ²=10.241 p=0.002 Total Parkinson score 2-9 20 (33.3%) 52 (78.8%) χ²=5.385 ns Total Parkinson score 12-14 0 2 (3.03%) χ²=5.385 ns Laita et al, 2007 Endocrine Side Effects ENDOCRINE SIDE EFFECTS NORMAL RANGE SHORT-TERM LONG-TERM EXPOSURE Prolactin 2-20 ng/dL 34.2 (SD 22.6) 25.8 (SD 24.4) Glycosylated hemoglobin 3-6.5% total Hb 4.6 (SD 0.3) 4.7 (SD 0.37) Thyroid hormone T4 0.8-2 ng/dL 1.5 (SD 0.9) 1.4 (SD 1.3) TSH 0.5-4.5 ng/dL 1.8 (SD 0.8) 2.8 (SD 1.2) -Prolactin levels were elevated in 78.6% of the sample in short-term group, and in 48.5% in the longer-term group (χ²= 7.892, p=0.019) -In the longer-term group, treatment with risperidone correlated with prolactin levels (p=0.021). Laita et al, 2007 DESARROLLO DEL ENSAYO Fase 1 (8 semanas) Grupo A: EFA-3(DHA+EPA+VIT E) Firma CI s0 s2 s4 s6 s8 Lavado (2 semanas) Fase 2 (8 semanas) Grupo B: EFA-3 (DHA+EPA+VIT E) s10 s12 s14 s16 s18 Selección Fase 2 (8 semanas) Grupo A: Placebo ( aceite inerte+ VIT E) Fase 1 (8 semanas) Grupo B: Placebo ( aceite inerte+ VIT E) Firma CI s0 s2 s4 s6 s8 s10 s12 s14 s16 s18 ECG Analítica, constantes vitales, medidas antropométricas CGI, ABC, SRS, FADS, MEDFICTS, Omega 3 fatty acid inventory, UKU Analítica, constantes vitales, medidas antropométricas CGI, ABC, SRS, FADS, MEDFICTS, Omega 3 fatty acid inventory, UKU Cannabis Incremento en el uso de cannabis en adolescencia Estudios longitudinales demuestran por primera vez relación causa- efecto en la relación consumo de cannabis-psicosis El uso de cannabis se asocia con menor edad de inicio de los síntomas psicóticos, más síntomas positivos en el momento basal y mayor mejoría si cesa el consumo a los 6 meses después del episodio. Baeza et al, 2009 Psicoeducación • Intervención de tipo psicoeducativo comparada con “intervención no estructurada” • Dirigida a padres y pacientes adolescentes con primeros episodios psicóticos, en grupos separados • En ambos grupos, 3 sesiones individuales y 12 grupales que se añaden al tratamiento habitual. • Objetivos: 1. 2. 3. Comparar los cambios en la evolución de la enfermedad (recaídas…) Comparar los cambios en variables familiares (carga familiar…) Estimación del coste-beneficio Baeza et al, 2009 Heredabilidad de los trastornos mentales Trastorno Heredabilidad (%) Trastorno Heredabilidad (%) Alzheimer Alcoholismo Esquizofrenia Depresión mayor T Bipolar T Pánico > 60 50 - 60 60 - 89 70 - 89 33 - 75 45 TOC Rasgos personalidad Autismo TDAH Gilles Tourette Suicidio 45 - 65 40 - 50 90 80 - 90 90 45 Factores de riesgo para el desarrollo de esquizofrenia Familiar esquizofrénico • • • • • • Migración Estrés social Ciudad Drogas (cannabis) Obstétricos Fecha de nacimiento 0 10 Murray, 2002 20 30 40 50 Genéticos Sociales Tóxicos Lesionales ¿Infecciosos? Otros Estudios familiares en esquizofrenia Parentesco con el paciente esquizofrénico Genes compartidos: 0% población general 12,5% familiar de tercer grado 25% familiar de segundo grado 50% familiar de primer grado 100% gemelo monocigótico Riesgo de desarrollar esquizofrenia Gottesman, 1991 SGENE consortium Genome-wide scan for susceptibility genes conferring risk of schizophrenia Basic-Clinical colaboration Basic Research New therapeutic targets Data processing Diagnosis aid Training in neuroscience Clinical Investigation Predisposición genética Fenotipo vulnerable Hiperactividad eje HPA/CRF Traumas o acontecimient os vitales diarios en edad adulta Acontecimientos vitales negativos en la infancia (estrés) Hipocampo: Alteración de la neurogénesis Neurotoxicidad Locus Ceruleus: Hiperactividad NA Vunerabilidad al estrés y acontecimientos vitales Alteraciones biológicas Cambios emocionales y conductuales CONCLUSIONES • Es el producto de las patologías cerebrales diferentes o más complejo • Estudio de enfermedades complejas: marcadores de riesgo • Investigación colaborativa traslacional y multicéntrica ACKNOWLEDGEMENTS Clinical Psychiatrists: Mara Parellada Dolores Moreno Carmen Moreno Mar Alvarez Cloe Llorente Ana Espliego Nuria Martínez Miguel Moreno Psychologists: María Mayoral Jessica Merchán Marta Leiva Marta Rapado Research Nurses: Marisa Giráldez Cecilia Tapia Data Manager: Jose de Arriba CAFEPS group Patients and their families Adolescent Unit, Department of Psychiatry http://www.hggm.es/ua/ www.cibersam.es